Double-blind comparison of rectally administered diazepam to placebo for pediatric sedation: the cardiovascular response.

The sedative and cardiovascular effects of rectally administered diazepam (0.6 mg/kg) were compared to placebo in uncooperative children who required sedation during dental treatment. Twelve healthy preschool children, who required amalgam restorations, were treated during two standardized restorative appointments in a double-blind, crossover study. Blood pressure and pulse were obtained during four specified intervals during the appointment. The behavior of the children during the treatment visits was videotaped and later statistically analyzed using a kinesics/vocalization instrument. Behavioral ratings of cooperation were significantly improved during the treatment visit following diazepam. All interfering bodily movements, patient vocalizations and operator commands for the diazepam group were reduced significantly (p≤0.0001). No significant differences were observed for noninterfering behavioral response. Rectally administered diazepam did not alter blood pressure or pulse significantly in these sedated children when compared to the placebo. These findings indicate that rectal diazepam is an effective sedative agent with minimal effect on the cardiovascular system for the management of the young pediatric dental patient.

A review of the effects of Transcendental Meditation on cardiovascular disease

Cardiovascular disease (CVD) is the single greatest cause of death in the United States, accounting for nearly 2400 deaths each day. It is estimated that 79.4 million American adults have some form of the disease, and CVD mortality rates are greater than those of cancer, chronic lower respiratory diseases, accidents and diabetes mellitus combined. Psychosocial stress is a nontraditional risk factor for CVD, and can contribute to the clustering of traditional risk factors as well as to vascular manifestations of the disease. The Transcendental Meditation (TM) technique has been researched as a cost effective intervention aimed at decreasing psychosocial stress. This literature review attempts to analyze randomized controlled clinical trials of TM on cardiovascular disease outcomes. Eleven studies met inclusion criteria and are described below, with statistically significant positive outcomes observed in each study. Studies are grouped by primary outcome reported in the categories of cardiovascular function, blood pressure, and exercise tolerance. The TM intervention significantly decreased insulin resistance, heart rate variability, and carotid intima media thickness and improved exercise tolerance compared to control groups. Seven studies also reported significant decreases in blood pressure among hypertensive and normotensive subjects. Five studies focused solely on African American subjects, a population that has disproportionately higher rates of CVD and hypertension, and found significant improvements in CVD outcomes. Further research is recommended to establish the efficacy of TM on CVD outcomes. Future trials should include larger sample populations, wider ethnic distributions of subjects, and longer follow-up to ascertain the impact of this particular stress reduction technique on cardiovascular disease.^

Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies.

A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a "cosmopolitan" tagging approach to capture the genetic diversity across approximately 2,000 loci in populations represented in the HapMap and SeattleSNPs projects. The array content is informed by GWAS of vascular and inflammatory disease, expression quantitative trait loci implicated in atherosclerosis, pathway based approaches and comprehensive literature searching. The custom flexibility of the array platform facilitated interrogation of loci at differing stringencies, according to a gene prioritization strategy that allows saturation of high priority loci with a greater density of markers than the existing GWAS tools, particularly in African HapMap samples. We also demonstrate that the IBC array can be used to complement GWAS, increasing coverage in high priority CVD-related loci across all major HapMap populations. DNA from over 200,000 extensively phenotyped individuals will be genotyped with this array with a significant portion of the generated data being released into the academic domain facilitating in silico replication attempts, analyses of rare variants and cross-cohort meta-analyses in diverse populations. These datasets will also facilitate more robust secondary analyses, such as explorations with alternative genetic models, epistasis and gene-environment interactions.

A study of the relationship between physical activity and cardiovascular fitness and coronary heart disease risk factors in female adolescents

The association of measures of physical activity with coronary heart disease (CHD) risk factors in children, especially those for atherosclerosis, is unknown. The purpose of this study was to determine the association of physical activity and cardiovascular fitness with blood lipids and lipoproteins in pre-adolescent and adolescent girls.^ The study population was comprised of 131 girls aged 9 to 16 years who participated in the Children's Nutrition Research Center's Adolescent Study. The dependent variables, blood lipids and lipoproteins, were measured by standard techniques. The independent variables were physical activity measured as the difference between total energy expenditure (TEE) and basal metabolic rate (BMR), and cardiovascular fitness, VO$\rm\sb{2max}$(ml/min/kg). TEE was measured by the doubly-labeled water (DLW) method, and BMR by whole-room calorimetry. Cardiovascular fitness, VO$\rm\sb{2max}$(ml/min/kg), was measured on a motorized treadmill. The potential confounding variables were sexual maturation (Tanner breast stage), ethnic group, body fat percent, and dietary variables. A systematic strategy for data analysis was used to isolate the effects of physical activity and cardiovascular fitness on blood lipids, beginning with assessment of confounding and interaction. Next, from regression models predicting each blood lipid and controlling for covariables, hypotheses were evaluated by the direction and value of the coefficients for physical activity and cardiovascular fitness.^ The main result was that cardiovascular fitness appeared to be more strongly associated with blood lipids than physical activity. An interaction between cardiovascular fitness and sexual maturation indicated that the effect of cardiovascular fitness on most blood lipids was dependent on the stage of sexual maturation.^ A difference of 760 kcal/d physical activity (which represents the difference between the 25th and 75th percentile of physical activity) was associated with negligible differences in blood lipids. In contrast, a difference in 10 ml/min/kg of VO$\rm\sb{2max}$ or cardiovascular fitness (which represents the difference between the 25th and 75th percentile in cardiovascular fitness) in the early stages of sexual maturation was associated with an average positive difference of 15 mg/100 ml ApoA-1 and 10 mg/100 ml HDL-C. ^

The role of the experience and expression of anger in future cardiovascular profiles in young adolescents

Cardiovascular disease (CVD) is this nation's leading source of morbidity and mortality, with health disparities evident. Despite inconsistencies in the literature, there is a growing body of evidence that links anger and CV reactivity (CVR) to future CVD. Because CVD is a life-long process with beginnings in childhood, and because adolescents experience and express anger frequently, the need to understand the role that anger has in future CV profiles is important. If identifiable patterns are found, nursing interventions can be implemented at the most beneficial point in the lifespan. This study examined data collected as part of The Heartfelt Study (N = 374), which investigated anger in relation to 24-hour ambulatory blood pressure (BP) and CVR in a multi-ethnic (African, Hispanic, and European American) sample of adolescents (Time 1). This investigator conducted a follow-up for all The Heartfelt Study participants, 11 to 13 years old at the beginning of study, still in attendance at the middle school (N = 44) one year later (Time 2) to determine: (1) changes in anger over time were associated with changes in ambulatory CV profiles: systolic (SBP), diastolic (DBP), heart rate (HR), and pulse pressure (PP) over time; and (2) the extent to which CVR, initiated by talking about a recent anger-producing event, related to future ambulatory CV profiles. A mixed-effects regression for repeated measures was used to analyze the data and found that SBP reactivity at Time 1 was significantly (β = 0.2341, t = 5.91, p < 0.0001) associated with ambulatory SBP at Time 2 and PP reactivity at Time 1 was significantly (β = 0.1530, t = 5.70, p < 0.0001) associated with ambulatory PP at Time 2. Changes in anger over time were not associated with changes in ambulatory BP measures over time. Further research on anger and CVR among adolescents over longer periods of time is recommended. ^

Genome-wide gene-gene interaction analysis for cardiovascular disease

Numerous studies have been carried out to try to better understand the genetic predisposition for cardiovascular disease. Although it is widely believed that multifactorial diseases such as cardiovascular disease is the result from effects of many genes which working alone or interact with other genes, most genetic studies have been focused on identifying of cardiovascular disease susceptibility genes and usually ignore the effects of gene-gene interactions in the analysis. The current study applies a novel linkage disequilibrium based statistic for testing interactions between two linked loci using data from a genome-wide study of cardiovascular disease. A total of 53,394 single nucleotide polymorphisms (SNPs) are tested for pair-wise interactions, and 8,644 interactions are found to be significant with p-values less than 3.5×10-11. Results indicate that known cardiovascular disease susceptibility genes tend not to have many significantly interactions. One SNP in the CACNG1 (calcium channel, voltage-dependent, gamma subunit 1) gene and one SNP in the IL3RA (interleukin 3 receptor, alpha) gene are found to have the most significant pair-wise interactions. Findings from the current study should be replicated in other independent cohort to eliminate potential false positive results.^

Body mass index trajectories and predictors among 3rd to 12th graders using growth curve mixture modeling the Child and Adolescent Trial for Cardiovascular Health (CATCH) study

This dissertation examined body mass index (BMI) growth trajectories and the effects of gender, ethnicity, dietary intake, and physical activity (PA) on BMI growth trajectories among 3rd to 12th graders (9-18 years of age). Growth curve model analysis was performed using data from The Child and Adolescent Trial for Cardiovascular Health (CATCH) study. The study population included 2909 students who were followed up from grades 3-12. The main outcome was BMI at grades 3, 4, 5, 8, and 12. ^ The results revealed that BMI growth differed across two distinct developmental periods of childhood and adolescence. Rate of BMI growth was faster in middle childhood (9-11 years old or 3rd - 5th grades) than in adolescence (11-18 years old or 5th - 12th grades). Students with higher BMI at 3rd grade (baseline) had faster rates of BMI growth. Three groups of students with distinct BMI growth trajectories were identified: high, average, and low. ^ Black and Hispanic children were more likely to be in the groups with higher baseline BMI and faster rates of BMI growth over time. The effects of gender or ethnicity on BMI growth differed across the three groups. The effects of ethnicity on BMI growth were weakened as the children aged. The effects of gender on BMI growth were attenuated in the groups with a large proportion of black and Hispanic children, i.e., “high” or “average” BMI trajectory group. After controlling for gender, ethnicity, and age at baseline, in the “high BMI trajectory”, rate of yearly BMI growth in middle childhood increased 0.102 for every 500 Kcals increase (p=0.049). No significant effects of percentage of energy from total fat and saturated fat on BMI growth were found. Baseline BMI increased 0.041 for every 30 minutes increased in moderate-to-vigorous PA (MVPA) in the “low BMI trajectory”, while Baseline BMI decreased 0.345 for every 30 minutes increased in vigorous PA (VPA) in the “high BMI trajectory”. ^ Childhood overweight and obesity interventions should start at the earliest possible ages, prior to 3rd grade and continue through grade school. Interventions should focus on all children, but specifically black and Hispanic children, who are more likely to be highest at-risk. Promoting VPA earlier in childhood is important for preventing overweight and obesity among children and adolescents. Interventions should target total energy intake, rather than only percentage of energy from total fat or saturated fat. ^

Environmental tobacco smoke exposure, respiratory and cardiovascular health in restaurant and bar workers in Mexico

Environmental tobacco smoke (ETS) is a well established health hazard, being causally associated to lung cancer and cardiovascular disease. ETS regulations have been developed worldwide to reduce or eliminate exposure in most public places. Restaurants and bars constitute an exception. Restaurants and bar workers experience the highest ETS exposure levels across several occupations, with correspondingly increased health risks. In Mexico, previous exposure assessment in restaurants and bars showed concentrations in bars and restaurants to be the highest across different public and workplaces. Recently, Mexico developed at the federal level the General Law for Tobacco Control restricting indoors smoking to separated areas. AT the local level Mexico City developed the Law for the Protection of Non-smokers Health, completely banning smoking in restaurants and bars. Studies to assess ETS exposure in restaurants and bars, along with potential health effects were required to evaluate the impact of these legislative changes and to set a baseline measurement for future evaluations.^ A large cross-sectional study conducted in restaurants and bars from four Mexican cities was conducted from July to October 2008, to evaluate the following aims: Aim 1) Explore the potential impact of the Mexico City ban on ETS concentrations through comparison of Mexico City with other cities. Aim 2). Explore the association between ETS exposure, respiratory function indicators and respiratory symptoms. Aim 3). Explore the association between ETS exposure and blood pressure and heart rate.^ Three cities with no smoking ban were selected: Colima (11.5% smoking prevalence), Cuernavaca (21.5% smoking prevalence) and Toluca (27.8% smoking prevalence). Mexico City (27.9% smoking prevalence), the only city with a ban at the time of the study, was also selected. Restaurants and bars were randomly selected from municipal records. A goal of 26 restaurants and 26 bars per city was set, 50% of them under 100 m2. Each establishment was visited during the highest occupancy shift, and managers and workers answered to a questionnaire. Vapor-phase nicotine was measured using passive monitors, that were activated at the beginning and deactivated at the end of the shift. Also, workers participated at the beginning and end of the shift in a short physical evaluation, comprising the measurement of Forced Expiratory Volume in the first second (FEV1) and Peak Expiratory Flow (PEF), as well as blood pressure and heart rate.^ A total of 371 establishments were invited, 219 agreed to participate for a 60.1% participation rate. In them, 828 workers were invited, 633 agreed to participate for a 76% participation rate. Mexico City had at least 4 times less nicotine compared to any of the other cities. Differences between Mexico City and other cities were not explained by establishment characteristics, such as ventilation or air extraction. However, differences between cities disappeared when ban mechanisms, such as policy towards costumer's smoking, were considered in the models. An association between ETS exposure and respiratory symptoms (cough OR=1.27, 95%CI=1.04, 1.55) and respiratory illness (asthma OR=1.97, 95%CI=1.20, 3.24; respiratory illness OR=1.79, 95%CI=1.10, 2.94) was observed. No association between ETS and phlegm, wheezing or respiratory infections was observed. No association between ETS and any of the spirometric indicators was observed. An association between ETS exposure and increased systolic and diastolic blood pressure at the end of the shift was observed among non-smokers (systolic blood pressure beta=1.51, 95%CI=0.44, 2.58; diastolic blood pressure beta=1.50, 95%CI=0.72, 2.28). The opposite effect was observed in heavy smokers, were increased ETS exposure was associated with lower blood pressure at the end of the shift (systolic blood pressure beta=1.90, 95%CI=-3.57, -0.23; diastolic blood pressure beta=-1.46, 95%CI=-2.72, -0.02). No association in light smokers was observed. No association for heart rate was observed. ^ Results from this dissertation suggest Mexico City's smoking ban has had a larger impact on ETS exposure. Ventilation or air extraction, mechanisms of ETS control suggested frequently by tobacco companies to avoid smoking bans were not associated with ETS exposure. This dissertation suggests ETS exposure could be linked to changes in blood pressure and to increased respiratory symptoms. Evidence derived from this dissertation points to the potential negative health effects of ETS exposure in restaurants and bars, and provides support for the development of total smoking bans in this economic sector. ^

The combined effect of pravastatin and aspirin on clinical cardiovascular events

The 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, can achieve significant reductions in plasma low-density lipoprotein (LDL)-cholesterol levels. Experimental and clinical evidence now shows that some statins interfere with formation of atherosclerotic lesions independent of their hypolipidemic properties. Vulnerable plaque rupture can result in thrombus formation and artery occlusion; this plaque deterioration is responsible for most acute coronary syndromes, including myocardial infarction (MI), unstable angina, and coronary death, as well as coronary heart diseaseequivalent non-hemorrhagic stroke. Inhibition of HMG-CoA reductase has potential pleiotropic effects other than lipid-lowering, as statins block mevalonic acid production, a precursor to cholesterol and numerous other metabolites. Statins' beneficial effects on clinical events may also thus involve nonlipid-related mechanisms that modify endothelial function, inflammatory responses, plaque stability, and thrombus formation. Aspirin, routinely prescribed to post-MI patients as adjunct therapy, may potentiate statins beneficial effects, as aspirin does not compete metabolically with statins but acts similarly on atherosclerotic lesions. Common functions of both medications include inhibition of platelet activity and aggregation, reduction in atherosclerotic plaque macrophage cell count, and prevention of atherosclerotic vessel endothelial dysfunction. The Cholesterol and Recurrent Events (CARE) trial provides an ideal population in which to examine the combined effects of pravastatin and aspirin. Lipid levels, intermediate outcomes, are examined by pravastatin and aspirin status, and differences between the two pravastatin groups are found. A modified Cox proportional-hazards model with aspirin as a time-dependent covariate was used to determine the effect of aspirin and pravastatin on the clinical cardiovascular composite endpoint of coronary heart disease death, recurrent MI or stroke. Among those assigned to pravastatin, use of aspirin reduced the composite primary endpoint by 35%; this result was similar by gender, race, and diabetic status. Older patients demonstrated a nonsignificant 21% reduction in the primary outcome, whereas the younger had a significant reduction of 43% in the composite primary outcome. Secondary outcomes examined include coronary artery bypass graft (38% reduction), nonsurgical bypass, peripheral vascular disease, and unstable angina. Pravastatin and aspirin in a post-MI population was found to be a beneficial combination that seems to work through lipid and nonlipid, anti-inflammatory mechanisms. ^

The effects of obesity in critical illness

Obesity continues to cripple the United States in terms of increasing health care expenditures and its rising rate of prevalence in epidemic proportions. The comorbidities associated with obesity have continued to represent some of the most deadly chronic health diseases. The most vulnerable subpopulation, the critically ill, suffers from not only the comorbid conditions but also the complications encountered within their specialized care. Taking into account the rising prevalence rates of obesity and critical care patients, it has come to the attention of many researchers to measure the trends associated with these two health conditions. Hospital mortality was found to be lower in higher BMI groups whereas there was no difference between BMI groups for ICU mortality. Length of stay and mechanical ventilation were both higher for obese rather than non-obese patients. The most prevalent disease states among the obese critically injured was cardiovascular and pulmonary disease. In conclusion, obesity is not independently associated with increased ICU mortality, but the comorbidities linked to obesity prove a greater threat to vitality.^

The effect of yoga on cardiovascular health as measured by heart rate variability in a sample of breast cancer patients

The study is a three-armed randomized controlled trial comparing values for heart rate variability (HRV), a measure of cardiovascular health, throughout a yoga intervention of breast cancer patients undergoing radiotherapy. Patients attended either a yoga (n=45), stretch, (n=46), or control (n=42) condition 3 times per week for 6 weeks of radiation. Electrocardiograms (ECGs) were conducted on each participant to provide the values necessary for HRV analysis. Analyses focused on examining scores for those participants with HRV baseline values considered to be below the cutoff point for healthy HRV levels, defined by the authors as below the cutpoint of 68 ms. From the entire sample of 133 with available baselines, 26 yogis, 26 stretchers, and 23 controls were determined to be “pathologic” in terms of HRV, and selected for follow-up analysis at 3 weeks and then again at 6 weeks. Though no statistically significant differences were found between either group means at each timepoint or group change score means, the yoga group had consistently higher mean score and mean change scores. These findings are suggestive and indicate the need to refine the use of ECGs and HRV analysis programs to more accurately and comprehensively assess the effects of yoga on cardiovascular health in cancer patients.^